In this Veterans Affairs ORD Shared Equipment Evaluation Program (ShEEP) application, we are requesting instrumentation for high throughput single-cell genomics (Fluidigm C1 Single-Cell Auto Prep System, BioMark, and Illumina NextSeq 550 Sequencing System) to evaluate cell-specific genomic, epigenetic, and transcriptomic variations in diseases of high relevance to the VA mission. This instrumentation will dramatically enhance Veterans Affairs (VA) and non-VA investigators to investigate mechanisms of disease progression at the level of single cells. Although dramatic advances have been made in the last decade in our ability to process and sequence DNA and RNA in bulk populations of cells, until recently our understanding of significant variations in genomic and transcriptomic information at the level of the single cell has been limited. For instance, major insights into fundamental biological processes such as normal development and tumor evolution secondary to oncogenic potential of single cells can only be garnered from a detailed understanding of genomic, epigenomic, and transcriptional variation at the single-cell level. In addition, certain pathogenic cells are so rare that single-cell approaches become essential to their identification and characterization. Our Genomics Core is part of an ongoing collaboration to enhance the academic and administrative ties between the Northport Veterans Affairs Medical Center (NVAMC) and its affiliated Stony Brook University School of Medicine (SBUSM). This new instrumentation will be housed in NVAMC and this strategic location allows easy access to the instruments for both VA and SBUSM investigators. The location of this Core will encourage further collaboration between VA investigators at Northport and their University colleagues at Stony Brook. Technical support is available through the Genomics Core on a fee-for-service basis to support both VA researchers and their collaborators. In addition, we have assembled a team of experts for bioinfomatics support. Many of the VA investigators including Drs. Mallipattu, Lin, McKinnon, Rohatgi, Miller, Arvanian, Del Poeta, and Obeid, whose research are supported by Merit Review Awards, and would significantly benefit from the acquisition and utilization of this instrumentation for high throughput single-cell genomics. Trained personnel in the Core can operate the instrument and provide technical support and we have outlined a plan to purchase service contracts to maintain the instrument. In this ShEEP application for high-throughput single cell genomics instrumentation, we also describe in detail the specifics of the instrumentation, justification of need, demonstrate the technical expertise to support the usage of the equipment, descriptions of the major and minor users, and the organizational plan for the utilization of the instrumentation. The long-term impact of this single-cell analysis instrumentation is that it will enhance the impact and further our currently funded VA Merit Review Awards. In addition, results acquired from single-cell genomics will generate new hypothesis and provide new avenues for future investigations in diseases that are highly relevant to the VA mission.